Hormone, toxins, interferon, neurotropic agents, and other bioactive ligands interact with cell surfaces to initiate their action on cells. One means these ligands can transmit information is by altering electrochemical ion gradients. In current projects, cells from target tissues and plasma membrane vesicles from these cells are being used to study effects on membrane potential, calcium, and proton fluxes. Effects of thyrotropin, tetanus toxin, and interferon on these parameters have been delineated. Tetanus toxin induces dose-dependent changes in the membrane potential and calcium fluxes of brain synaptosomes. The mechanisms of calcium accumulation by brain synaptosomal membrane vesicles have been characterized in order to define the site of tetanus toxin action and the role of the membrane in regulating intrasynaptosomal calcium. Interferon and thyrotropin, as early events, alter the membrane potential of cells which are biologically responsive. These effects are being related to the initiation of hormone, toxin, or interferon action at the plasma membrane level. Toxins are being studied as they are natural pathogenic agents which subvert normal hormonal regulatory mechanisms.